tbuckley/cabot-search huggingface dataset:
Racial disparities in cancer mortality in patients with gastrointestinal malignancies following Medicaid expansion.
Authors: Naveen Manisundaram, Rebecca A Snyder, Chung-Yuan Hu, Sandra R. DiBrito, George J. Chang
Journal: Journal of Clinical Oncology (2023)

6546 Background: Racial minorities experience disparities in receipt of cancer treatment and survival. The optional Medicaid expansion provision of the Affordable Care Act provided federal funding to participating states to improve healthcare access for disadvantaged populations by expanding Medicaid eligibility criteria. This study aimed to investigate the effect of Medicaid expansion on racial disparities in mortality among patients with gastrointestinal malignancies. Methods: A cross-sectional cohort study of patients with pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and gastric adenocarcinoma (GC) of any stage was conducted using the National Cancer Database (2009-2019). Difference-in-difference analysis (DID) was performed to compare adjusted 2-year mortality separately among Black and White patients residing in Medicaid expansion states (MES) and non-expansion states (non-MES) before (2009-2013) and after (2014-2019) expansion. Differences in receipt of surgery and chemotherapy were also evaluated. Results: A total of 86,052 patients were included for analysis, including 19,188 patients with PDAC, 60,404 with CRC, and 6,460 with GC. Two-year mortality decreased among Black patients with PDAC residing in MES compared to non-MES following expansion (DID -9.4%, p&lt;0.001) (Table). Mortality also decreased among Black and White patients with CRC in MES compared to non-MES following expansion (DID -4.2%, p &lt; 0.001 and -2.9%, p = 0.047). Among patients with GC, Black patients in MES experienced a marked reduction in mortality compared to non-MES (DID -7.7%, p = 0.07). Both Black and White stage 3-4 PDAC patients had an increase in receipt of chemotherapy in MES following expansion (DID 3.7%, p=0.28 and DID 2.7%, p=0.20). Rates of surgery, but not chemotherapy receipt, increased among Black patients with stage 4 CRC in MES following expansion (DID 5.7%, p=0.03 and 1.0%, p=0.66, respectively). A greater increase in receipt of chemotherapy was observed among Black patients with stage 4 GC in MES than in non-MES (DID 11%, p=0.06). Conclusions: Medicaid expansion was associated with a greater reduction in 2-year mortality rates for Black patients residing in MES than for those in non-MES. Existing racial disparities in mortality remained the same or worsened in non-MES but in almost all cases were mitigated in MES following Medicaid expansion. [Table: see text]
Early real-world (RW) experience with a multi-cancer early detection (MCED) test.
Authors: Candace Westgate, Dallas Kingsbury, Martin Poliak, Jordan Lipton, Matthew McMillin, Louis B. Malinow, Marc Ryan Matrana, John F. Beausang, Geoff Stanley, Rita Shaknovich, Jeffrey M. Venstrom, Kathryn Kurtzman, Vershalee Shukla
Journal: Journal of Clinical Oncology (2023)

10519 Background: An MCED test (Galleri, GRAIL, LLC, Menlo Park, CA) intended to complement recommended screening has been in clinical use since 04/2021. Here, we report RW clinical experience across age, sex, ordering site, and use case with the initial ~53,000 tests. Methods: This cell-free DNA-based MCED test uses a targeted methylation assay and a machine learning classification algorithm to detect a cancer signal (CS) and predict CS origin (CSO). This report includes tests returned from 04/20/2021 to 12/31/2022 on individuals aged ≥22 years (yrs) and excludes tests from clinical studies and sites limiting external data sharing, and repeat tests. Systematic collection of outcomes for cases with a “CS detected” (CSD) result was completed for a limited subset and continues via a rigorously controlled quality assurance (QA) program. Results: Tests were ordered and processed from across all US states (results returned, 98.9%; mean turnaround time, 6.7 business days). Among the 53,134 tests with results returned, CSD rate (CSDR) was was 1.0% (95% CI, 0.9-1.0; 510/53134), generally higher in males (1.1% [1.0-1.2; 313/29201]) vs females (0.8% [0.7-0.9; 197/23933]), and comparable to expected CSDR (males 1.07%; females 0.96%) as modeled based on MCED test performance and cancer incidence from SEER. CSDR increased with age (Table), which was a significant predictor of CSDR (p &lt; 2e-13). In males and females, 67.4% and 61.9% of CSOs represented cancers without (w/o) recommended population screening, respectively. Early data from the QA program from an initial limited subset of CSD cases showed that a CSD result was associated with a diagnosis of invasive cancer across multiple cancers (eg, anus, breast, esophagus, head and neck, liver/bile duct, lymphoma, ovary, pancreas, plasma cell neoplasm, prostate, sarcoma), including stage I and II cancers. Conclusions: RW experience with the MCED test was consistent with previous large-scale clinical studies with an average CSDR of 1.0%, which increased with age. The test detected a CS and predicted CSO across multiple cancers, including early-stage cancers and cancers w/o recommended screening. This indicates that the MCED test can reliably detect a CS, which is essential to support population screening. Follow-up of CSD cases is ongoing through the QA program and will allow for future reporting of RW outcomes. [Table: see text]
A phase 3 trial of fianlimab (anti–LAG-3) plus cemiplimab (anti–PD-1) versus pembrolizumab in patients with previously untreated unresectable locally advanced or metastatic melanoma.
Authors: Ana Baramidze, Miranda Gogishvili, Tamta Makharadze, Mariam Zhvania, Khatuna Vacharadze, John Crown, Tamar Melkadze, Omid Hamid, Georgina V. Long, Caroline Robert, Mario Sznol, Hector Martinez-Said, Jayakumar Mani, Usman Chaudhry, Mark Salvati, Israel Lowy, Matthew G. Fury, Giuseppe Gullo
Journal: Journal of Clinical Oncology (2023)

TPS9602 Background: Fianlimab (anti-lymphocyte activation gene 3 [LAG-3]) and cemiplimab (anti- programmed cell death-1 [PD-1]) are both high-affinity, fully human, IgG4 monoclonal antibodies (Abs). Concurrent blockade of anti-LAG-3 and anti-PD-1 has shown enhanced efficacy (increase in progression free survival [PFS]) in advanced melanoma (Mel). We previously presented data from a phase 1 study showing a 63.8% objective response rate (ORR) across two separate cohorts of advanced PD-(L)1 naïve metastatic Mel patients (pts) treated with fianlimab plus cemiplimab with an acceptable risk-benefit profile. Methods: This is a randomized, double-blind, phase 3 study to evaluate fianlimab plus cemiplimab compared to pembrolizumab in pts with previously untreated unresectable locally advanced or metastatic Mel (NCT05352672). This study will be conducted globally, at approximately 200 sites. Key inclusion criteria are: (1) ≥12 years of age; (2) histologically confirmed unresectable Stage III and Stage IV (metastatic) Mel (3) no prior systemic therapy for advanced unresectable disease, prior (neo)adjuvant therapies are allowed with treatment/disease-free interval of 6 months; (4) measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1; (5) valid LAG-3 results; (6) Eastern Cooperative Oncology Group performance status (PS) of 0 or 1 (for adult pts), Karnofsky PS ≥70 (pts ≥16 years) or Lansky PS ≥70 (pts &lt; 16 years); and (7) anticipated life expectancy of at least 3 months. There are 4 arms to the study: (1) Arm A: fianlimab (1600 mg) + cemiplimab (350 mg) every 3 weeks (Q3W), intravenously (IV); (2) Arm A1: fianlimab (400 mg) + cemiplimab (350 mg) Q3W, IV; (3) Arm B: pembrolizumab (200 mg Q3W, IV) + saline/dextrose placebo (placebo); (4) Arm C: cemiplimab (350 mg Q3W, IV) + placebo. The trial is expected to enroll approximately 1590 pts. The primary endpoint is progression-free survival. The key secondary endpoints are overall survival and objective response rate. The additional secondary endpoints include disease control rate, duration of response, safety, pharmacokinetics of cemiplimab and fianlimab, and immunogenicity (incidence and titer of anti-drug Abs and neutralizing Abs). The study is currently open for enrollment. Clinical trial information: NCT05352672 .
Patterns of actionable biomarker testing in lung cancer patients: Disparity or an opportunity for improvement.
Authors: Robert Asa Horn, Dushyant Pawar, Kavya Bharathidasan, Jasmine Kaur Sekhon, Shabnam Rehman
Journal: Journal of Clinical Oncology (2023)

e21211 Background: In 2018, lung cancer represented about 13% of new cancer diagnosis but was still the leading cause of cancer deaths at 25%. In the last five years, rates of new cases of lung cancer have decreased by 11% and survival has increased 21% nationally; largely due to advancements in screening, diagnosis and expanding treatment modalities, including targeted therapies geared toward specific molecular alterations. Despite these advancements, there are still shortcomings in terms of next generation sequencing (NGS) utilization for detection of molecular aberrations. A recent query of 37,925 patients with stage IV non-small cell lung cancer (NSCLC), diagnosed between 2010 and 2018 discovered that only 22% of all patients had any molecular testing. Only 3% of these patients received any form of targeted therapy. This further illustrates the ongoing gap between molecular diagnostics and its clinical utilization. Methods: Our project serves to assess this shortcoming in our patient population. In this retrospective chart review and quality improvement project, the goal was to identify the limitations that led to delays or omittance of timely NGS in patients with newly diagnosed NSCLC. Under an IRB approval, a system was created where once a biopsy was confirmed to be NSCLC, tissue was sent for NGS. Prior to this intervention, molecular testing had to be ordered by an Oncologist after the patient was seen in clinic, generally during their first outpatient appointment or when discussed in multidisciplinary meetings. Additionally, testing was shifted from individual molecular studies, which would frequently exhaust tissue sample, to only comprehensive panels. Results: The charts of 194 patients with newly diagnosed NSCLC between 2014 and 2022 were analyzed. Of these patients, 125 patients (64.4%) had completion of at least one molecular test. 36 patients (18.6%) had only been tested for programmed death-ligand 1 (PDL1) and 33 patients (17.0%) had no immunohistochemical or molecular testing following biopsy results. The time from biopsy to completion of molecular testing was compared to 34 patients following implementation of our protocol. The median time from biopsy to availability of results was 29 days before our intervention and decreased to 23 days afterwards. Additionally, molecular testing increased to 100% in our newly diagnosed NSCLC patient population. Conclusions: As the genomic revolution continues and the importance of targeted therapy for NSCLC in both the adjuvant and metastatic setting progresses, timely next generation sequencing will be paramount for optimal treatment selection. Our project shows that through the implementation of systems codeveloped between medical oncology and anatomic pathology, turnaround times of molecular testing can be greatly improved and widely implemented.
Analysis of sarcoma outcomes at a metropolitan area safety net hospital.
Authors: Mariam Haji, Marwa Elsayed, Anshul Raman, Samia Asif, An-Lin Cheng, Sheshadri Madhusudhana, Anuj Shrestha
Journal: Journal of Clinical Oncology (2023)

e18688 Background: Sarcomas are a group of heterogenous tumors with diverse histopathological types. They account for less than 1% of adult solid tumors (1) . The estimated new cases were 13,190 with 5,130 estimated deaths in 2022 (2) . Survival is largely determined by presence of metastasis on diagnosis, grade, site, and size of the tumor (3) . Data over 19 years in our safety net hospital were analyzed including demographic data, disease characteristics and treatment modalities in association with overall survival. Methods: All patients diagnosed with sarcoma from 1998 to 2017 were included in the analysis. Patients were categorized by insurance status, stage, site, grade, pain on presentation, and treatment modalities. Survival analysis and Kaplan-Meier curves were conducted to examine the relation between patient demographics and survival. Results: Of 163 patients included in the analysis, 54% were insured and 46% were uninsured. Uninsured patients had a higher overall survival rate compared to insured patients (HR = 0.49, CI 0.38-0.90, p = 0.014). Regarding race, 55% of patients were white, 35.6% were black and 9.2% patients were identified as other races. There was no difference in overall survival between different ethnicities. Regarding gender, 61.3% were males and 38.7% were females with no statistically significant difference in survival. Compared to stage I, stage III were 2.28 times (CI 1.27-4.08, p = 0.005) and stage IV were 5.76 times (CI 3.16-10.05, p &lt; 0.001) more likely to die. There was no statistically significant improvement in overall survival in patients who underwent chemotherapy or radiotherapy. However, surgical intervention was associated with improved survival and patients were three times more likely to survive (0.3, CI 0.18-0.5, p &lt; 0.001). Analysis also showed no statistically significant difference in survival in patients presenting with pain. Conclusions: Insured patients have better outcomes overall than uninsured patients in sarcomas (4) . Nevertheless, within safety-net-hospitals, all patients receive necessary treatment regardless of insurance status. We found that in our institution, insurance may factor in delaying treatment due to hurdles such as prior authorizations, co-pays and coverage disruptions (5) . Conversely, uninsured patients can begin appropriate treatment without such delays which could explain difference in survival rates. Additional studies are needed to identify the possible effects of insurance and pinpoint its burden on survivorship. [Table: see text]
External validation of venous thromboembolism risk prediction models in patients with multiple myeloma in a community setting: A retrospective cohort study.
Authors: Chidambaram Ramasamy, Abinesh Sekar, Harinivaas Shanmugavel Geetha, Madhan Srinivasan Kumar, Masood Pasha Syed, Kala Seetharaman, Ahmad Daniyal Siddiqui, George M. Abraham
Journal: Journal of Clinical Oncology (2023)

e20027 Background: Newly diagnosed Multiple Myeloma (MM) patients have a 10 to 20 times higher risk of developing venous thromboembolism (VTE) than the general population. Three risk prediction models have been recently established to ascertain the degree of VTE risk: SAVED (Surgery, Asian race, VTE history, Elderly and Dexamethasone), IMPEDE VTE (Immunomodulatory drugs (IMiD), BMI, Pelvic fracture, Erythropoietin stimulating agent, Dexamethasone/Doxorubicin, Asian Ethnicity, VTE history, Tunneled line, Existing thromboprophylaxis) and PRISM scores (Prior VTE, Race, IMiD, Surgery, Metaphase Cytogenetics). Our primary objective was to assess the external validity of three VTE risk prediction models in a community hospital setting. Methods: All consecutive newly diagnosed MM treated at Saint Vincent Hospital from 1/1/2012 to 12/22/2022 were included in our analysis. Patients receiving therapeutic anticoagulation for other indications or a diagnosis of VTE within 6 months prior to MM diagnosis were excluded. Variables were collected by retrospective chart review at the time of MM treatment initiation. Model discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Logistic regression was used to calculate the odds ratio (OR) of VTE occurrence with candidate variables in the risk prediction model. Results: The 160 patients with newly diagnosed MM and available data on VTE occurrence were included. The median age of our cohort at treatment initiation was 74 years (range 31-96); 55% were male, and 75% were Caucasians. IMiD-based induction regimen was used in 68.1 % of patients. The median SAVED score was 1 (IQR:0-2), IMPEDE VTE was 4 (IQR: 2-6), and PRISM score was 2 (IQR: 0-2). The most common thromboprophylactic agent used was aspirin (53.8%). The median time to VTE from induction was 4.8 months. The cumulative incidence of VTE at 12 months was 13.1%. Each 1-point increase in the score was associated with a significantly higher chance of VTE occurrence across all three models (Table). Factors significantly associated with the development of VTE were prior VTE history (OR:2.28, 95% CI:1.31-3.97,p = 0.003) and age greater than 80 years (OR:4.03, 95% CI:1.47-11.02,p = 0.006). Conclusions: Our findings suggest that all three PRISM (AUROC = 0.70), SAVED (AUROC = 0.72), and IMPEDE VTE (AUROC = 0.73) scores could statistically predict VTE outcomes in our patient population. The inclusion of more parameters in the IMPEDE VTE score may have led to its outperformance in risk stratification. [Table: see text]
Understanding cancer treatment decision making among cancer survivors.
Authors: Brennan Streck, Jacqueline B. Vo, Carolyn Brandt, William Klein, Paul Han, Rebecca Ferrer, Arielle Samantha Gillman
Journal: Journal of Clinical Oncology (2023)

e24076 Background: Nearly 20% of U.S. cancer survivors develop late cardiovascular disease (CVD) as a result of cardiotoxic cancer treatments. Patients and providers may consider alternative treatment options to lower cardiotoxicity risk, which may present a trade-off between reducing relatively near-term relapse/recurrence vs. preventing long-term CVD. Patients’ decision-making processes (e.g., delay discounting, risk perceptions for CVD vs. cancer) may affect such choices. However, these decision-making factors are not well understood in this context; nor is their association with treatment selection. Methods: In a cross-sectional survey using the online survey vendor Prolific, we recruited 443 U.S. cancer survivors (any type.) Using logistic regression, we assessed how survivors’ risk perceptions (deliberative, affective, and intuitive) for cancer vs. CVD were associated with decisions between two hypothetical cancer treatments involving different risk tradeoffs: Treatment 1: 5% chance of near-term cancer recurrence &amp; 10% chance of CVD; Treatment 2: 10% chance of near-term cancer recurrence &amp; 5% chance of CVD. We explored effects of delay discounting by randomizing participants to information describing immediate vs. delayed (10 years post-treatment) development of CVD. Results: Survivors ( Mage = 48, range 18-93) were, on average, 10.8 years from diagnosis. More survivors ( 72% v. 28%) chose Treatment 1 (lower cancer recurrence risk but higher risk of cardiotoxicity) than Treatment 2 (lower risk of cardiotoxicity but higher risk of cancer recurrence) . Immediacy of CVD development (immediate vs. delayed) was not associated with treatment selection (p = 0.12.) Modeling separately, higher levels of affective risk perception (“worry”) about cancer, but not worry about CVD, was associated with increased odds of choosing Treatment 1 ( OR= 1.25, p= 0.014.). Modeled together, cancer worry was associated with increased odds, whereas CVD worry was associated with decreased odds, of choosing Treatment 1 ( OR-cancer= 1.35, p= 0.002; OR-CVD= 0.76, p= 0.011). Neither deliberative nor experiential risk perceptions were significantly associated with treatment choice. Conclusions: Cancer survivors were more likely to select treatment that minimizes cancer recurrence rather than comparative CVD—regardless of the described immediacy of cardiotoxicity. Further, treatment decision also depended upon both cancer- and CVD-related worry but not deliberative or experiential risk perceptions. Comparatively to CVD, cancer is often more affectively-laden, especially among cancer survivors. These results suggest that in treatment discussions, clinicians may need to address not only the probabilities of treatment outcomes, but patients’ relative worries about cancer and cardiotoxicity.
Factors associated with overall and cancer specific mortality in primary cardiac sarcoma.
Authors: Ayrton Bangolo, Pierre Fwelo, Vignesh Nagesh, Amer Jarri, Angel Ann Chacko, Shraboni Dey, Tracy Ann Proverbs-Singh, Adam Atoot
Journal: Journal of Clinical Oncology (2023)

e23539 Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. Virtually all types of sarcomas have been reported in the heart. For most types, only isolated case reports have been described. We used a nationally representative database to evaluate the independent prognostic factors amongst patients with PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p value &lt; 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors.All statistical tests were performed by using Software STATA 16.1. The SEER database is a publicly available dataset for which there was no need for IRB approval. Results: The male gender (50.83%), and non-Hispanic whites (58.84%) were the most represented groups in our cohort. The most encountered histologic subtype was angiosarcoma (42.51%), which represented nearly half the cases. Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and PCS related mortality among US patients between 2000 and 2017 demonstrated Higher overall mortality in age 80+ (HR = 13.261, 95% CI 5.839-30.119, p = 0), followed by age 60-79 (HR = 1.916, 95% CI 1.213-3.025, p = 0.005); and advanced disease with distant metastasis (HR = 2.013, 95% CI 1.355-2.99, p = 0.001), followed by regional involvement (HR = 1.518, 95% CI 1.041-2.214, p = 0.03). Lower OM rate was observed in patients with rhabdomyosarcoma (HR = 0.364, 95% CI 0.154-0.86, p = 0.021) and widowed (HR = 0.506, 95% CI 0.263-0.977, p = 0.042). Age 80+ (HR = 11.177, 95% CI 4.449-28.08, p = 0) and advanced disease with distant metastases (HR = 2.117, 95% CI 1.37-3.271, p = 0.001) have the highest cancer specific mortality. Patients with rhabdomyosarcoma (HR = 0.344, 95% CI 0.128-0.929, p = 0.035) have a lower CSM. Conclusions: In this United States population-based retrospective cohort study using the SEER database, we found that age at diagnosis and advanced disease at diagnosis were independent factors predicting poor prognosis. Furthermore, patients with rhabdomyosarcoma had a lower mortality compared to other histologic subtypes. Surgical resection of the primary tumor did not significantly impact the overall mortality or the cancer-specific mortality.